Abstract | BACKGROUND AND PURPOSE: Compounds targeting epigenetic events of tumours are likely to be an important addition to anticancer therapy. Histone deacetylase inhibitors (HDACI) have emerged as a promising novel class for therapeutic interventions associated with cancer, and many of them are currently in clinical investigation. Here, we assessed a novel hydroxamate-based HDACI, LW479, in breast cancer progression and explored its underlying mechanism(s). EXPERIMENTAL APPROACH: LW479 was identified using the HDACI screening kit. Western blot and flow cytometry were used to analyse the biological effects of LW479 as a novel HDACI. The effects of LW479 were assessed in mouse models of spontaneous and experimental breast cancer. Co-immunoprecipitation, immunofluorescent staining and chromatin immunoprecipitation assays along with immunohistochemical analysis, were used to elucidate the molecular basis of the actions of LW479. KEY RESULTS: CONCLUSIONS AND IMPLICATIONS: Our data have elucidated the mechanisms underlying the inhibition by LW479 of tumour growth and metastasis, in models of breast cancer with aberrant EGFR expression. LW479 could be a candidate drug for breast cancer prevention.
|
Authors | Jingjie Li, Tao Zhang, Feifei Yang, Yuan He, Fujun Dai, Dan Gao, Yihua Chen, Mingyao Liu, Zhengfang Yi |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 172
Issue 15
Pg. 3817-30
(Aug 2015)
ISSN: 1476-5381 [Electronic] England |
PMID | 25884486
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2015 The British Pharmacological Society. |
Chemical References |
- 6-(2-(2-(3-bromophenyl)-4-oxo-3-thiazolidinyl)phenoxy)-N-hydroxylhexanamide
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Thiazolidines
- Vorinostat
- ErbB Receptors
|
Topics |
- Animals
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, enzymology, metabolism, pathology)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Disease Progression
- Down-Regulation
(drug effects)
- ErbB Receptors
(biosynthesis, genetics)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Histone Deacetylase Inhibitors
(pharmacology)
- Humans
- Hydroxamic Acids
(adverse effects, pharmacology)
- Mice
- Neoplasm Invasiveness
(pathology)
- Promoter Regions, Genetic
(genetics)
- Thiazolidines
(adverse effects, pharmacology)
- Vorinostat
|